title: Celecoxib improves host defense through prostaglandin inhibition during Histoplasma capsulatum infection.
abstract: Prostaglandins act as mediators of inflammation and, similar to cytokines, function as immune modulators during innate and adaptive immune responses. Therefore, using a pharmacological inhibitor, celecoxib, we investigated the role of prostaglandins in host defense against Histoplasma capsulatum infection in C57BL/6 mice. Our results showed that treatment with celecoxib inhibited cyclooxygenase 2, reduced the total fungal burden, and reduced the concentration of PGE2, cytokines, lymphocytes, neutrophils, and mononuclear cells in the bronchoalveolar space and lung parenchyma. In addition, celecoxib treatment increased the synthesis of nitric oxide, IFN- γ, LTB4, and the phagocytic capacity of alveolar macrophages. Moreover, celecoxib treatment increased the survival of mice after infection with a lethal inoculum of H. capsulatum. These results suggest that prostaglandins alter the host immune response and play an important role in the pathogenesis of histoplasmosis. Thus, the inhibition of prostaglandins could be a valuable immunomodulatory strategy and antifungal therapy for histoplasmosis treatment.
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Priscilla Aparecida Tartari
authors.initials: PA
authors.lastname: Pereira
authors.forename: Bruno Caetano
authors.initials: BC
authors.lastname: Trindade
authors.forename: Adriana
authors.initials: A
authors.lastname: Secatto
authors.forename: Roberto
authors.initials: R
authors.lastname: Nicolete
authors.forename: Camila
authors.initials: C
authors.lastname: Peres-Buzalaf
authors.forename: Simone Gusmão
authors.initials: SG
authors.lastname: Ramos
authors.forename: Ruxana
authors.initials: R
authors.lastname: Sadikot
authors.forename: Claudia da Silva
authors.initials: Cda S
authors.lastname: Bitencourt
authors.forename: Lúcia Helena
authors.initials: LH
authors.lastname: Faccioli
mesh_terms: D000818:Animals; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D006658:Histoplasma / Q000187:drug effects / Q000472:pathogenicity*; D006660:Histoplasmosis / Q000188:drug therapy* / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D011720:Pyrazoles / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D007975:Leukotriene B4; D009569:Nitric Oxide; D007371:Interferon-gamma; D000068579:Celecoxib